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NEWS

Gene Signature Could Revolutionize Cancer Care

Discovery should help doctors tailor treatment to specific tumor type

By Amanda Gardner/HealthDay, June 2, 2005

Scientists have identified an 11-gene "signature" in cancer
tumors that appears to predict prognosis in at least 10 types of malignancies.

If it passes further testing, the signature may help doctors and patients
decide on therapies that suit particular cancer types, a giant step forward
in the emerging era of tailored treatments.

"It's a very exciting study," said Dr. Jay Brooks, chairman
of hematology/oncology at the Ochsner Clinic Foundation in New Orleans.
"It's using molecular genetics to try to predict which patients will
respond or won't respond to current therapies. Then we would be able to
offer patients who may have a particularly resistant type of a cancer
other therapeutic options."

"It will allow each individual to predict with 95 percent or greater
accuracy what would be the likelihood of successful therapy," added
study author Dr. Gennadi Glinsky, an associate professor of molecular
genetics and cancer biology at Sidney Kimmel Cancer Center in San Diego.

"If your cancer can be cured with just surgery alone, then you just
go on and take it and have a great deal of expectation for a happy life,"
Glinsky explained. "If your disease profile belongs to the 30 percent
that will fail therapy, you will know this well in advance and be able
to choose advanced treatment or even novel therapy. We will be able to
focus on those who need our focus and let those patients who will be cured
with existing therapy go on with their lives."

The findings appear in the June 1 issue of the Journal of Clinical Investigation.

The study was based on the relatively new concept that tumors contain
a certain proportion of stem cell-like cells along with other cells. These
cells, it is hypothesized, are responsible for tumor progression and spread.
The BMI-1 pathway in which the cells are activated could provide crucial
information about the tumor.

The researchers identified the genetic signature in a mouse cancer model,
as well as in tumors from human prostate cancer patients.

They then looked at the prognostic power of this signature in more than
1,000 individuals diagnosed with several different types of cancer: prostate,
breast, lung, ovarian, bladder, lymphoma, mesothelioma,
acute myeloid leukemia and two types of brain tumors.

When this signature was present in primary tumors, patients experienced
a shorter time to disease recurrence, and were also more likely to experience
cancer spread and to die after being treated.

The findings also seemed to bolster the idea that a tumor's potential
to spread is determined relatively early in the course of the malignancy.

At the very least, the authors of an accompanying commentary state, the
signature may mean that doctors can differentiate patients with a poor
prognosis from those with a better prognosis and adjust treatment accordingly.

The findings may also change the process of development of new cancer
therapies, Glinsky said. Right now, many cancers have very high five-year
survival rates, meaning that any trial to prove the superiority of a new
treatment is both long and costly.

But with this signature, pharmaceutical companies should be able to try
out new therapies on a pre-selected group of patients, cutting down on
both time and cost, he said.

"We now need to bring it down to earth and develop tests that would
be applicable in every hospital," he said.

One company has already licensed the technology required to detect this
signature, and Glinsky said he is pushing for clinical trials to start
this summer.

"If everything holds water, we might have a test within a year,"
he said. "That's my hope."

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